Modulation of rat monocyte/macrophage innate functions by increasing intensities of swimming exercise is associated with heat shock protein status

Abstract

Moderate exercise positively impacts innate immune functions, bringing about a better resistance against infections and general immunosurveillance. Exercise of high workloads (i.e., high intensity and/or duration) such as elite marathon, on the other hand, may have detrimental effects over immune function, but neither how long nor how intense should be the exercise sessions to be deleterious is known, this being a matter of intense dispute. Exercise is, at the same time, one of the most powerful inducers of the 70 kDa family of heat shock proteins (HSPAs, formerly known as HSP70s), which are protein chaperones characterized by a marked anti-inflammatory potency, when located intracellularly (iHSPA), but may act as pro-inflammatory cytokines if in the extracellular space (eHSPA). The above observations led us to suppose that short-term exercise could impose long-lasting effects on macrophage function that should be related to the eHSPA-to-iHSPA ratio, viz. H-index. Sedentary adult male Wistar rats were then submitted to 20 min swimming sessions with an overload (as a percentage of body weight attached to the tail base) of either 2, 4, 6, or 8 %. Control animals were maintained at rest in shallow water. Monocyte/macrophage functions (phagocytic capacity, nitric oxide [NO], and hydrogen peroxide [H2O2]) were assessed just after and 12 h after exercise and compared with HSPA status and oxidative stress markers. The results showed that exercise increased phagocytosis and H2O2 immediately after the bouts in a workload-dependent way. This was accompanied by increased H-index but no alteration in the redox status. Enhanced phagocytic capacity persisted for up to 12 h, when a marked rise in NO production was also observed, but H-index resumes its control values, suggesting that immune alertness returned to basal levels. Of note was the detection of the cognate form of eHSPA (encoded by hspa8 gene and formerly known as HSP73) in the rat sera. In total, acute exercise may evoke 12 h long workload-dependent effects associated with HSPA status.

Acute exercise boosts cell proliferation and the heat shock response in lymphocytes: correlation with cytokine production and extracellular-to-intracellular HSP70 ratio

“…However, only HSPA1A ELISA kits have been sufficiently tested worldwide and proved to be of enough sensitivity (pg/mL range) to detect minute HSP70 quantities in culture media and sera. Additionally, previous results from this laboratory (Schöler et al 2016) have indicated that the principal eHSP70 forms (HSPA1A and HSPA8) are secreted in similar amounts. Therefore, it was assumed that HSPA1A is representative of total eHSP70 secretion.…”

“…The adaptation period consisted of keeping the animals for 8 min in individual swimming pool chambers (20 × 20 × 56 cm) filled with water at 31 ± 1°C (50cm depth), for three consecutive days, without any overload (avoiding any type of exercise training). Afterwards, overnight-fed animals (five per group) were randomly assigned for each round of swimming experiments according to exercise burden imposed by a lead overload (2, 4, 6 or 8% of body weight) attached to the base of the tail and were, then, submitted to an acute swimming exercise bout of 20 min under the same circumstances as during the adaptation, one rat per chamber, as described (Rossato et al 2014) with the adaptations introduced elsewhere (Schöler et al 2016). Control animals remained at rest in shallow water (5-cm depth; 31 ± 1°C, 20 min) during each experiment.…”

“…Swimming exercise is assumed to be a judicious choice to study the physiological impacts of physical exercise in rats, particularly by virtue of this influence on sympathetic nervous system (Baptista et al 2008), whose activation is tightly involved in stress response and immune surveillance (Schöler et al 2016;Rossato et al 2014;Mastorakos et al 2005;Febbraio and Pedersen 2005;Hackney 2006). Although treadmill running could be another choice, cardiovascular findings indicate that swimming and running protocols are not comparable (Nunes et al 2015), while swimming exercise is a more uniform type of exercise for rats because it does not necessarily involve Bstop-and-go^activity such as that found with treadmill running (Kregel et al 2006).…”

“…Consequently, the ratio between eHSP70 and iHSP70 (R = [eHSP70]/[iHSP70]) correlates with organismal immunoinflammatory balance, whereas the rate of variation in R ratios between different conditions (a.k.a. H-index of HSP70 status) is regarded as an index of changes in overall immunoinflammatory balance (Krause et al 2015a(Krause et al , 2015bLeite et al 2016;Schöler et al 2016;Krause and Rodrigues-Krause 2011). Therefore, in the present study, we investigated, in the rat model, whether acute exercise bouts of different intensities could influence the HS response of lymphocytes, which are a main source of both eHSP70 and iHSP70 under stressful situations (Hunter-Lavin et al 2004;Ireland et al 2007).…”

Screening and Function Analysis of MicroRNAs Involved in Exercise Preconditioning-Attenuating Pathological Cardiac Hypertrophy

“…14) However, the mechanism involved in EPinduced cardio-protection still remains controversial, such as increased heat shock protein production, increased cardiac antioxidant capacity, and improvement in ATPdependent potassium channel function. [15][16][17] In the present study, we focused on the differentially expressed miRNAs during EP-attenuating cardiac hypertrophy, and we analyzed the function annotation of their potential target genes. The result would provide valuable clues for the internal mechanism of miRNA-mediated regulation of cardiac hypertrophy.…”